PMID- 28273460
OWN - NLM
STAT- MEDLINE
DCOM- 20171128
LR  - 20211204
IS  - 2211-1247 (Electronic)
VI  - 18
IP  - 10
DP  - 2017 Mar 7
TI  - Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway.
PG  - 2464-2479
LID - S2211-1247(17)30239-5 [pii]
LID - 10.1016/j.celrep.2017.02.041 [doi]
AB  - The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical 
      signals in response to extracellular matrix (ECM) cues. However, the identity and 
      nature of regulators in the ECM and the precise pathways relaying 
      mechanoresponsive signals into intracellular sensors remain unclear. Here, we 
      uncover a functional link between the ECM proteoglycan Agrin and the 
      transcriptional co-activator YAP. Importantly, Agrin transduces matrix and 
      cellular rigidity signals that enhance stability and mechanoactivity of YAP 
      through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling 
      pathways. Agrin antagonizes focal adhesion assembly of the core Hippo components 
      by facilitating ILK-PAK1 signaling and negating the functions of Merlin and 
      LATS1/2. We further show that Agrin promotes oncogenesis through YAP-dependent 
      transcription and is clinically relevant in human liver cancer. We propose that 
      Agrin acts as a mechanotransduction signal in the ECM.
CI  - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Chakraborty, Sayan
AU  - Chakraborty S
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. 
      Electronic address: sayanc@imcb.a-star.edu.sg.
FAU - Njah, Kizito
AU  - Njah K
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
FAU - Pobbati, Ajaybabu V
AU  - Pobbati AV
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
FAU - Lim, Ying Bena
AU  - Lim YB
AD  - Infectious Diseases Interdisciplinary Research, Singapore-MIT Alliance for 
      Research and Technology, 1 CREATE Way, Singapore 138602, Singapore.
FAU - Raju, Anandhkumar
AU  - Raju A
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
FAU - Lakshmanan, Manikandan
AU  - Lakshmanan M
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
FAU - Tergaonkar, Vinay
AU  - Tergaonkar V
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
FAU - Lim, Chwee Teck
AU  - Lim CT
AD  - Infectious Diseases Interdisciplinary Research, Singapore-MIT Alliance for 
      Research and Technology, 1 CREATE Way, Singapore 138602, Singapore; Department of 
      Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, 
      Singapore 117583, Singapore; Mechanobiology Institute, National University of 
      Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
FAU - Hong, Wanjin
AU  - Hong W
AD  - Institute of Molecular and Cell Biology, Agency for Science, Technology and 
      Research (A( *)STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore. 
      Electronic address: mcbhwj@imcb.a-star.edu.sg.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Agrin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Transcription Factors)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (YAP1 protein, human)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
SB  - IM
CIN - Trends Cancer. 2017 Apr;3(4):247-248. PMID: 28718435
MH  - 14-3-3 Proteins/metabolism
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Agrin/*metabolism
MH  - Animals
MH  - Carcinogenesis
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cytoskeleton/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Female
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - Focal Adhesions/metabolism
MH  - Humans
MH  - *Mechanotransduction, Cellular
MH  - Mice, Nude
MH  - Phosphoproteins/*metabolism
MH  - Protein Binding
MH  - Protein Stability
MH  - *Signal Transduction
MH  - Transcription Factors
MH  - YAP-Signaling Proteins
OTO - NOTNLM
OT  - Agrin
OT  - YAP/TAZ
OT  - extracellular matrix
OT  - focal adhesions
OT  - hippo pathway
OT  - integrins
OT  - liver cancer
OT  - mechanotransduction
EDAT- 2017/03/09 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/03/09 06:00
PHST- 2016/04/19 00:00 [received]
PHST- 2016/12/28 00:00 [revised]
PHST- 2017/02/13 00:00 [accepted]
PHST- 2017/03/09 06:00 [entrez]
PHST- 2017/03/09 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
AID - S2211-1247(17)30239-5 [pii]
AID - 10.1016/j.celrep.2017.02.041 [doi]
PST - ppublish
SO  - Cell Rep. 2017 Mar 7;18(10):2464-2479. doi: 10.1016/j.celrep.2017.02.041.